Microfluidic chip and application thereof

Abstract

The application provides a microfluidic chip, which comprises a sample inlet cavity, a first heating cavity, a second heating cavity, a collection cavity, microfluidic channels for connecting the cavities and a heating mechanism. The microfluidic chip of the application transfers a traditional synthesis process to the microfluidic chip. Based on microfluidic fluid control technology, the reaction volume of each component is accurately controlled by designing the geometric structure of the microfluidic channel. The synthesis process parameters are controlled by using laminar flow diffusion and micro-mixing technology, so that the particle size and uniformity of the obtained magnetic nanoparticles are controlled. Compared with the traditional synthesis method, the microfluidic chip synthesis method has the characteristics of uniform solution mixing, reduction of magnetic nanoparticle agglomeration, simple equipment, no need for a large space and small volume of used solution.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of microfluidic technology, and particularly relates to a microfluidic chip and application thereof. BACKGROUND

[0002] Magnetic nanoparticles refer to particles with a particle size of less than 100 nm, and the main component is metal oxide. Since the physicochemical properties of nanoparticles depend on their size and morphology, it is particularly important to synthesize nanoparticles with controllable size and shape. As an important part of the synthesis of magnetic microspheres, the uniformity and size of magnetic nanoparticles greatly affect the magnetic response and particle size of the magnetic beads.

[0003] Traditional methods for synthesizing magnetic nanoparticles include co-precipitation, microemulsion, thermal decomposition, and hydrothermal method, most of which are through physical mixing of starting reactions, particle nucleation, particle growth, and particle formation. And it is necessary to control the particle size by changing the reaction parameters. Since the traditional method for synthesizing nanoparticles is complicated, it is easy to cause inconsistent local conditions in the synthesis process, and it is difficult to control the uniformity and batch difference of the synthesized particles. SUMMARY

[0004] Therefore, the present application provides a microfluidic chip and a method for synthesizing magnetic nanoparticles using the chip. The method can conveniently and quickly synthesize magnetic nanoparticles with high uniformity, thereby solving the technical problems of the traditional method for synthesizing nanoparticles, which is complicated, and it is difficult to control the uniformity and batch difference of the synthesized particles.

[0005] The technical solution of the present application is to provide a microfluidic chip:

[0006] The microfluidic chip comprises a sample inlet cavity, a first heating cavity, a second heating cavity, a collection cavity, a microfluidic channel for connecting the cavities, and a heating machine.

[0007] The sample inlet cavity comprises a first sample inlet cavity, a second sample inlet cavity, a third sample inlet cavity, and a fourth sample inlet cavity.

[0008] The first heating cavity, the second heating cavity, and the collection cavity are sequentially connected by the microfluidic channel.

[0009] The first sample inlet cavity and the second sample inlet cavity are located upstream of the first heating cavity and are connected to the first heating cavity.

[0010] The third sample inlet cavity is connected to the microfluidic channel connecting the first heating cavity and the second heating cavity.

[0011] The fourth sample inlet cavity is located downstream of the first heating cavity and upstream of the second heating cavity, and is connected to the second heating cavity.

[0012] The heating mechanism is used for independently heating the first heating cavity and the second heating cavity.

[0013] In one embodiment, the first sample inlet cavity and the second sample inlet cavity are merged in a microfluidic channel upstream of the first heating cavity and then communicated with the first heating cavity.

[0014] In one embodiment, the microfluidic channel communicated with the fourth sample inlet cavity is merged with the microfluidic channel for communicating the first heating cavity and the second heating cavity and then communicated with the second heating cavity.

[0015] 5In one embodiment, the microfluidic channel for communicating the first heating cavity and the second heating cavity is in a serpentine shape.

[0016] In one embodiment, the third sample inlet cavity is connected to the most upstream position of the bending part of the serpentine-shaped microfluidic channel for communicating the first heating cavity and the second heating cavity.

[0017] 0In one embodiment, the second heating cavity has multiple independent sub-cavities inside, and the solution entering the second heating cavity is divided into multiple sub-cavities for heating and then merged into the collection cavity.

[0018] In one embodiment, the number of sub-cavities is 6-10, and the width of each sub-cavity is uniform.

[0019] The application also provides a method for synthesizing magnetic nanoparticles by using the microfluidic chip as described above.

[0020] In one embodiment, the method for synthesizing magnetic nanoparticles comprises:

[0021] FeCl3 solution and FeCl2 solution are respectively added to the first sample inlet cavity and the second sample inlet cavity, a solution with pH greater than 7 is added to the third sample inlet cavity, and an oil phase is added to the fourth sample inlet cavity.

[0022] The first heating cavity and the second heating cavity are heated.

[0023] The reaction product is collected from the collection cavity.

[0024] In one embodiment, when the first heating cavity and the second heating cavity are heated, the temperature in the first heating cavity is controlled to be 45-55℃, and the temperature in the second heating cavity is controlled to be 65-75℃.

[0025] In one of the embodiments, the sample injection flow rate of the first sample injection chamber is 0.4 mL / min-0.6 mL / min, the sample injection flow rate of the second sample injection chamber is 0.2 mL / min-0.3 mL / min, the sample injection flow rate of the third sample injection chamber is 0.4 mL / min-0.6 mL / min, and the sample injection flow rate of the fourth sample injection chamber is 0.5 mL / min-1.5 mL / min.

[0026] In one of the embodiments, the solution with pH greater than 7 includes one or both of 2% ammonia water or NaOH solution in volume concentration.

[0027] In one of the embodiments, the oil phase includes one or both of liquid paraffin and silicone oil.

[0028] The application also provides a magnetic nanoparticle prepared by the method for synthesizing magnetic nanoparticles according to any one of claims 8-12.

[0029] The application transfers the traditional synthesis process onto a microfluidic chip, controls the particle size and uniformity of the magnetic nanoparticles by controlling the synthesis process parameters based on the microfluidic fluid control technology, through designing the geometric structure of the microfluidic channel, through accurately controlling the reaction volume of each component, through laminar diffusion and micro-mixing technology. Compared with the traditional synthesis method, the microfluidic chip synthesis method has the following advantages: 1. The solution is more uniform, through designing the mixing area on the microfluidic chip, through the change from laminar flow to turbulent flow, the solution mixing is more uniform than the traditional mechanical stirring; 2. The microfluidic chip can separate each stage of the synthesis of the magnetic nanoparticles, and there is no interference between them, which can reduce the agglomeration of the magnetic nanoparticles; 3. The microfluidic chip synthesis method requires simple equipment, does not require a large space, and uses a small volume of solution, which is very convenient for adjusting the experimental conditions, and is very suitable for optimizing the experimental conditions in the early stage; 4. Through the design of the microfluidic chip, multiple chips can be cascaded, multiple conditions can be optimized at the same time, and the yield can be improved. BRIEF DESCRIPTION OF DRAWINGS

[0030] Figure 1 Figure 1 is a structural schematic diagram of a microfluidic chip;

[0031] Figure 2 Figure 2 is a TEM image of the magnetic nanoparticles synthesized in Example 1;

[0032] Figure 3 Figure 3 is a TEM image of the magnetic nanoparticles synthesized in Example 2;

[0033] Figure 4 Figure 4 is a TEM image of the magnetic nanoparticles synthesized in Example 3;

[0034] Figure 5 TEM image of magnetic nanoparticles synthesized for Example 4;

[0035] Figure 6 TEM image of magnetic nanoparticles synthesized for Example 5;

[0036] Figure 7 TEM image of magnetic nanoparticles synthesized for Comparative Example 1;

[0037] Figure 8 TEM image of magnetic nanoparticles synthesized for Comparative Example 2;

[0038] Figure 9 TEM image of magnetic nanoparticles synthesized for Comparative Example 3;

[0039] Figure 10 TEM image of magnetic nanoparticles synthesized for Comparative Example 4. DETAILED DESCRIPTION

[0040] The present application will be further described below in conjunction with the embodiments and examples. It should be understood that these embodiments and examples are only used to illustrate the present application and not intended to limit the scope of the present application, and the purpose of providing these embodiments and examples is to make the disclosure of the present application more thoroughly and comprehensively understood. It should also be understood that the present application can be implemented in many different forms and is not limited to the embodiments and examples described herein, and those skilled in the art can make various modifications or changes without departing from the spirit of the present application, and the equivalent forms obtained thereby also fall within the scope of the present application. In addition, in the following description, a large number of specific details are given in order to provide a more complete understanding of the present application, and it should be understood that the present application can be implemented without one or more of these details.

[0041] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.

[0042] Terminology

[0043] As used herein, "combinations thereof", "any combinations thereof", "any combination thereof" and the like include all suitable combinations of any two or more of the listed items.

[0044] In the present application, "suitable combinations", "suitable ways", "any suitable ways" and the like mean that the technical solutions of the present application can be implemented, the technical problems of the present application can be solved, and the expected technical effects of the present application can be achieved.

[0045] In the present application, "preferably", "more preferably", "more preferably", "suitable" are only to describe the better effect of the embodiment or example, it should be understood that it does not constitute a limitation on the scope of protection of the present application.

[0046] In the present application, "further", "more further", "in particular" and the like are used to describe the purpose, indicating the difference in content, but should not be understood as a limitation on the scope of protection of the present application.

[0047] In the present application, the numerical interval (i.e. the numerical range) is involved, such as no special instructions, the optional numerical distribution in the above numerical interval is regarded as continuous, and includes the two numerical endpoints (i.e. the minimum value and the maximum value) of the numerical range, and each numerical value between the two numerical endpoints. If no special instructions are given, when the numerical interval is only directed to the integer in the numerical interval, including the two endpoint integers of the numerical range and each integer between the two endpoints, in this paper, it is equivalent to directly listing each integer, such as t is an integer selected from 1-10, which means that t is an integer selected from the integer group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10. In addition, when multiple ranges are provided to describe characteristics or characteristics, these ranges can be combined. In other words, unless otherwise indicated, the range disclosed herein should be understood to include any and all subranges included therein.

[0048] In the present application, the technical features described in an open way include both the closed technical solution consisting of the listed features and the open technical solution including the listed features.

[0049] Microfluidics: microfluids are manipulated by micron channels or even nanochannels, so as to realize micro-reaction on the chip, so as to synthesize materials and screen substances by less reagents and samples.

[0050] TEM: Transmission Electron Microscope (TEM), which can see the fine structure smaller than 0.2um under optical microscope, which is called submicrostructure or ultrastructure. In order to see these structures, it is necessary to select a shorter wavelength light source to improve the resolution of the microscope. In 1932, Ruska invented a transmission electron microscope with electron beam as light source. The wavelength of electron beam is much shorter than that of visible light and ultraviolet light, and the wavelength of electron beam is inversely proportional to the square root of the voltage of the emitted electron beam, that is, the higher the voltage, the shorter the wavelength. The resolution of TEM can reach 0.2nm.

[0051] For example, the compound of formula (I) is a compound of formula (Ia): Figure 1As shown, the present application provides a microfluidic chip 10, which comprises a sample inlet chamber, a first heating chamber 115, a second heating chamber 116, a collection chamber 117, microfluidic channels 118 for connecting the chambers, and a heating mechanism.

[0052] The sample inlet chamber comprises a first sample inlet chamber 111, a second sample inlet chamber 112, a third sample inlet chamber 113, and a fourth sample inlet chamber 114.

[0053] The first heating chamber 115, the second heating chamber 116, and the collection chamber 117 are sequentially connected by the microfluidic channels 118.

[0054] The first sample inlet chamber 111 and the second sample inlet chamber 112 are located upstream of the first heating chamber 115 and are both connected to the first heating chamber. The solutions in the first sample inlet chamber 111 and the second sample inlet chamber 112 can be mixed before entering the first heating chamber 115, or can be mixed after entering the first heating chamber 115 separately.

[0055] The third sample inlet chamber 113 is connected to the microfluidic channel for connecting the first heating chamber 115 and the second heating chamber 116.

[0056] The fourth sample inlet chamber 114 is located downstream of the first heating chamber 115 and upstream of the second heating chamber 116, and is connected to the second heating chamber 116.

[0057] The heating mechanism is used to independently heat the first heating chamber 115 and the second heating chamber 116.

[0058] In a specific example, the first sample inlet chamber 111 and the second sample inlet chamber 112 are merged in the microfluidic channel upstream of the first heating chamber 115 and then connected to the first heating chamber 115.

[0059] In a specific example, the microfluidic channel 118 connected to the fourth sample inlet chamber 114 is merged with the microfluidic channel for connecting the first heating chamber 115 and the second heating chamber 116 and then connected to the second heating chamber 116.

[0060] Optionally, the microfluidic channel for connecting the first heating chamber 115 and the second heating chamber 116 is in the shape of a serpentine tube.

[0061] In a specific example, the connection position of the third sample inlet chamber 113 to the microfluidic channel for connecting the first heating chamber 115 and the second heating chamber 116 is located at the most upstream position of the bending part of the serpentine-shaped microfluidic channel.

[0062] Further optionally, the second heating chamber 116 has multiple independent sub-chambers inside, and the solution entering the second heating chamber 116 is divided into multiple sub-chambers for heating and then merged into the collection chamber.

[0063] In one specific example, the number of sub-chambers is 6-10, and the width of each sub-chamber is uniform. For example, the number can be 6, 7, 8, 9, or 10.

[0064] The application also provides a method for synthesizing magnetic nanoparticles, which uses the microfluidic chip as described above for synthesis. The method for synthesizing magnetic nanoparticles includes adding FeCl3 solution and FeCl2 solution to the first sample inlet chamber 111 and the second sample inlet chamber 112 respectively, adding a solution with a pH greater than 7 to the third sample inlet chamber 113, and adding an oil phase to the fourth sample inlet chamber 114.

[0065] The first heating chamber 115 and the second heating chamber 116 are subjected to heating treatment, and the reaction product is collected from the collection chamber 117.

[0066] In one specific example, when the first heating chamber and the second heating chamber are subjected to heating treatment, the temperature in the first heating chamber 115 is controlled to be 45-55°C, and the temperature in the second heating chamber 116 is controlled to be 65-75°C. For example, the temperature in the first heating chamber 115 is 45°C, 46°C, 47°C, 48°C, 49°C, 50°C, 51°C, 52°C, 53°C, 54°C, or 55°C. For example, the temperature in the second heating chamber 116 is 65°C, 66°C, 67°C, 68°C, 69°C, 70°C, 71°C, 72°C, 73°C, 74°C, or 75°C.

[0067] In one specific example, the sample inlet flow rate of the first sample inlet chamber 111 is 0.4-0.6 mL / min, for example, 0.4 mL / min, 0.5 mL / min, or 0.6 mL / min.

[0068] In one specific example, the sample inlet flow rate of the second sample inlet chamber 112 is 0.2-0.3 mL / min, for example, 0.2 mL / min, 0.25 mL / min, or 0.3 mL / min.

[0069] In one specific example, the sample inlet flow rate of the third sample inlet chamber 113 is 0.4-0.6 mL / min, for example, 0.4 mL / min, 0.5 mL / min, or 0.6 mL / min.

[0070] In one specific example, the sample inlet flow rate of the fourth sample inlet chamber 114 is 0.5-1.5 mL / min, for example, 0.5 mL / min, 1 mL / min, or 1.5 mL / min.

[0071] In one specific example, the solution with a pH greater than 7 is one or both of 2% ammonia water or NaOH solution in terms of volume concentration.

[0072] In one specific example, the oil phase is one or both of liquid paraffin and silicone oil.

[0073] The application also provides a magnetic nanoparticle, which is prepared by the method for synthesizing magnetic nanoparticles according to any one of claims 8-12.

[0074] The embodiments of the application will be described in detail below with reference to the examples. It should be understood that the examples are only used to illustrate but not to limit the scope of the application. The experimental methods in the following examples without specific conditions are preferably referred to the instructions given in the application, and can also be performed according to the experimental manuals or conventional conditions in the art, or according to the conditions suggested by the manufacturers, or according to the known experimental methods in the art.

[0075] In the following specific examples, the measurement parameters of the raw material components may have slight deviations within the weighing accuracy range if not otherwise specified. The temperature and time parameters allow acceptable deviations caused by the instrument testing accuracy or operation accuracy.

[0076] In the examples of the application, the high-concentration iron salt concentration range is 0.5M-2M, the medium-concentration iron salt concentration range is 0.05M-0.2M, and the low-concentration iron salt concentration range is 0.005M-0.02M.

[0077] The high-concentration NaOH concentration range is 0.5M-2M, the low-concentration NaOH concentration range is 0.05M-0.2M, and the low-concentration ammonia concentration range is 1%-5% by volume.

[0078] Example 1: Low-concentration iron salt + low-concentration ammonia + oil phase wrapping

[0079] I. An appropriate amount of FeCl3·6H2O and FeCl2·4H2O is weighed and prepared into a 0.01M solution. A 0.1M FeCl3 solution is injected into the first sample cavity at a rate of 0.5mL / min using a precision syringe pump, and a 0.1M FeCl2 solution is injected into the second sample cavity at a rate of 0.25mL / min, mixed through the first heating cavity, and heated to 50℃ by setting a heating patch in the first heating cavity.

[0080] II. A 2% by volume ammonia solution is passed through the third sample cavity at a flow rate of 0.5mL / min and mixed with the mixed solution in the first heating cavity at a rate of 2:1, and then fully mixed through the serpentine-shaped microchannel. An oil phase is then passed through the fourth sample cavity at a rate of 1mL / min to form a mixture of the FeCl3 solution, the FeCl2 solution, and the NaOH solution. At this time, two opposite velocity fields are formed during the droplet formation process, and the solution is mixed inside.

[0081] Three, after mixing into the second heating chamber 8 channels, each channel is divided equally to ensure uniform heating. The second heating chamber bottom is provided with a heating sheet, so that its temperature rises to 70°C. Subsequently, the droplets through the channel, the resulting magnetic nanoparticles are collected, the TEM of the magnetic nanoparticles obtained as shown in Figure 2 .

[0082] Example 2: low concentration of iron salt + low concentration of NaOH + oil phase package

[0083] I, weigh the appropriate amount of FeCl3·6H2O, FeCl2·4H2O, prepared into a 0.01M solution. Using a precision syringe pump to the first sample cavity with 0.5mL / min injection of 0.1M FeCl3 solution, the second sample cavity with 0.25mL / min speed injection of 0.1M FeCl2 solution, mixed through the first heating chamber, while the first heating chamber is set heating paste, the mixed solution is heated to 50°C.

[0084] II, the third sample cavity with 0.5mL / min flow rate of 0.1mol / L NaOH and the first heating chamber with the mixed liquid to 2:1 rate of fusion; through the serpentine tube type micro channel after mixing, through the fourth sample cavity with 1mL / min rate of oil phase, so as to form a mixture of FeCl3 solution, FeCl2 solution and NaOH solution, at this time, the droplet generation process will form two opposite direction velocity field, the internal will be mixed evenly.

[0085] III, after mixing into the second heating chamber 8 channels, each channel is divided equally to ensure uniform heating. The second heating chamber bottom is provided with a heating sheet, so that its temperature rises to 70°C. Subsequently, the droplets through the channel, the resulting magnetic nanoparticles are collected, the TEM of the magnetic nanoparticles obtained as shown in Figure 3 .

[0086] Example 3: medium concentration of iron salt + high concentration of NaOH + oil phase package:

[0087] I, weigh the appropriate amount of FeCl3·6H2O, FeCl2·4H2O, prepared into a 0.1M solution. Using a precision syringe pump to the first sample cavity with 0.5mL / min injection of 0.1M FeCl3 solution, the second sample cavity with 0.25mL / min speed injection of 0.1M FeCl2 solution, mixed through the first heating chamber, while the first heating chamber is set heating paste, the mixed solution is heated to 50°C.

[0088] II. The 1 mol / L NaOH solution is injected into the third inlet cavity at a flow rate of 0.5 mL / min and mixed with the mixed solution in the first heating cavity at a rate of 2:1. After sufficient mixing through the serpentine-shaped microchannel, the oil phase is injected into the fourth inlet cavity at a rate of 1 mL / min to form a mixture of the FeCl3 solution, the FeCl2 solution, and the NaOH solution. At this time, two opposite velocity fields are formed during the droplet generation process, and the solution is mixed uniformly inside.

[0089] III. After sufficient mixing, the solution enters the eight channels in the second heating cavity, each of which is equally divided to ensure uniform heating. A heating sheet is arranged at the bottom of the second heating cavity to raise the temperature to 70°C. Subsequently, the droplets pass through the channels, and the desired magnetic nanoparticles are collected. The TEM of the obtained magnetic nanoparticles is shown in FIG. 4. Figure 4

[0090] Example 4: Medium concentration of iron salt + high concentration of NaOH

[0091] I. An appropriate amount of FeCl3·6H2O and FeCl2·4H2O is weighed and prepared into a 0.1 M solution. The 0.1 M FeCl3 solution is injected into the first inlet cavity at a rate of 0.5 mL / min using a precision syringe pump, and the 0.1 M FeCl2 solution is injected into the second inlet cavity at a rate of 0.25 mL / min. The mixed solution is heated to 50°C in the first heating cavity by arranging a heating sheet.

[0092] II. The 1 mol / L NaOH solution is injected into the third inlet cavity at a flow rate of 0.25 mL / min and mixed with the mixed solution in the first heating cavity at a rate of 1:1. After sufficient mixing through the serpentine-shaped microchannel, the oil phase is injected into the fourth inlet cavity at a rate of 1 mL / min to form a mixture of the FeCl3 solution, the FeCl2 solution, and the NaOH solution.

[0093] III. After sufficient mixing, the solution enters the eight channels in the second heating cavity, each of which is equally divided to ensure uniform heating. A heating sheet is arranged at the bottom of the second heating cavity to raise the temperature to 70°C. Subsequently, the droplets pass through the channels, and the desired magnetic nanoparticles are collected. The TEM of the obtained magnetic nanoparticles is shown in FIG. 4. Figure 5

[0094] Example 5: High concentration of iron salt + high concentration of NaOH

[0095] ​​I. Take the appropriate amount of FeCl3 6H2O, FeCl2 4H2O, and prepare a 0.5M solution. Use a precision syringe pump to inject 0.1M FeCl3 solution into the first sample chamber at 0.5mL / min, and inject 0.1M FeCl2 solution into the second sample chamber at 0.25mL / min. Mix the solutions in the first heating chamber, and set the heating pad to heat the mixed solution to 50°C.

[0096] II. Pass 1M NaOH through the third sample chamber at a flow rate of 0.5mL / min, and mix it with the solution in the first heating chamber at a rate of 2:1. After thorough mixing through the serpentine-shaped microchannel, a mixture of FeCl3 solution, FeCl2 solution, and NaOH solution is formed.

[0097] III. After thorough mixing, the solution enters the second heating chamber through 8 channels, each of which is equally divided to ensure uniform heating. A heating pad is placed at the bottom of the second heating chamber to raise the temperature to 80°C. After the droplets pass through the channels, the desired magnetic nanoparticles are collected, and the TEM of the obtained magnetic nanoparticles is shown in Figure 6

[0098] Comparative Example 1: High concentration of iron salt + high concentration of NaOH

[0099] I. Take the appropriate amount of FeCl3 6H2O, FeCl2 4H2O, and prepare a 0.5M solution.

[0100] II. Take the appropriate amount of NaOH, and prepare a 1M solution.

[0101] III. Take 10mL FeCl2 solution and 20mL FeCl3 solution, and add them to a 250mL three-necked flask. Add magnetic stirring, and add 1M NaOH solution dropwise at a stirring speed of 400rpm, until the solution turns black and the pH is about 11.

[0102] III. Transfer the flask to an oil bath, and heat it to 70°C. Stir at 1200rpm for 1 hour.

[0103] IV. Transfer the solution to a 50mL centrifuge tube, and use a magnetic stand to separate the magnetic nanoparticles. Wash them once with anhydrous ethanol and once with deionized water. The obtained magnetic nanoparticles have a TEM as shown in Figure 7

[0104] Comparative Example 2: Medium concentration of iron salt + high concentration of NaOH

[0105] I. Take the appropriate amount of FeCl3 6H2O, FeCl2 4H2O, and prepare a 0.1M solution. ​​

[0106] II. Take the appropriate amount of NaOH, prepared into a 1M solution.

[0107] III. Take 10 mL FeCl2 solution, 20 mL FeCl3 solution into a 250 mL three-necked flask, add magnetic stirring, 400 rpm stirring speed under the drop of 1M NaOH solution, until the solution becomes black, pH about 11 or so.

[0108] III. The flask was transferred to the oil bath, heated to 70°C, 1200 rpm stirring for 1 hour.

[0109] IV. The solution was transferred to a 50 mL centrifuge tube, using a magnetic frame to separate magnetic nanoparticles, using anhydrous ethanol and deionized water each wash once. The magnetic nanoparticles can be obtained, the magnetic nanoparticles obtained TEM as shown in Figure 8 .

[0110] Comparative Example 2: medium concentration of iron salt + high concentration of NaOH

[0111] I. Take the appropriate amount of FeCl3·6H2O, FeCl2·4H2O, prepared into a 0.1M solution.

[0112] II. Take the appropriate amount of NaOH, prepared into a 1M solution.

[0113] III. Take 10 mL FeCl2 solution, 20 mL FeCl3 solution into a 250 mL three-necked flask, add magnetic stirring, 400 rpm stirring speed under the drop of 1M NaOH solution, until the solution becomes black, pH about 11 or so.

[0114] IV. The flask was transferred to the oil bath, heated to 70°C, 1200 rpm stirring for 1 hour.

[0115] V. The solution was transferred to a 50 mL centrifuge tube, using a magnetic frame to separate magnetic nanoparticles, using anhydrous ethanol and deionized water each wash once. The magnetic nanoparticles can be obtained, the magnetic nanoparticles obtained TEM as shown in Figure 7 .

[0116] Comparative Example 3: medium concentration of iron salt + medium concentration of NaOH

[0117] I. Take the appropriate amount of FeCl3·6H2O, FeCl2·4H2O, prepared into a 0.1M solution.

[0118] II. Take the appropriate amount of NaOH, prepared into a 0.1M solution.

[0119] III. Take 10 mL of FeCl2 solution and 20 mL of FeCl3 solution and add them to a 250 mL three-neck flask. Add magnetic stirring and drop 0.1 M NaOH solution at a stirring speed of 400 rpm until the solution turns black and the pH is about 11.

[0120] IV. Transfer the flask to an oil bath and heat to 70°C. Stir at 1200 rpm for 1 hour.

[0121] V. Transfer the solution to a 50 mL centrifuge tube. Separate the magnetic nanoparticles using a magnetic stand. Wash the nanoparticles once with anhydrous ethanol and once with deionized water. The magnetic nanoparticles obtained are shown in FIG. 2. Figure 9

[0122] Comparative Example 4: Low concentration of iron salt + low concentration of ammonia

[0123] I. Weigh an appropriate amount of FeCl3·6H2O and FeCl2·4H2O to prepare a 0.01 M solution.

[0124] II. Take 10 mL of FeCl2 solution and 20 mL of FeCl3 solution and add them to a 250 mL three-neck flask. Add magnetic stirring and drop 2% ammonia water at a stirring speed of 400 rpm until the solution turns black and the pH is about 11.

[0125] III. Transfer the flask to an oil bath and heat to 70°C. Stir at 1200 rpm for 1 hour.

[0126] IV. Transfer the solution to a 50 mL centrifuge tube. Separate the magnetic nanoparticles using a magnetic stand. Wash the nanoparticles once with anhydrous ethanol and once with deionized water. The magnetic nanoparticles obtained are shown in FIG. 2. Figure 10

[0127] According to the above experimental results, by using the synthesis technology of microfluidic chips, the experimental conditions (such as the concentration of iron salt and the type and concentration of added alkali) are optimized, which can realize the synthesis of magnetic nanoparticles with uniform particle size and good dispersity. In contrast, the particle size uniformity and dispersity of the microspheres synthesized by the conventional synthesis method are poor.

[0128] ​​The above-described embodiments only express several implementation manners of the present application, facilitate specific and detailed understanding of the technical solutions of the present application, but cannot be understood as a limitation on the patent protection scope of the present application. It should be noted that, for ordinary skilled persons in the art, several modifications and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application. In addition, it should be understood that, after reading the above teaching content of the present application, the skilled person in the art can make various modifications or modifications to the present application, and the equivalent forms obtained are also within the protection scope of the present application. It should also be understood that, on the basis of the technical solutions provided by the present application, the skilled person in the art obtains the technical solutions through logical analysis, reasoning or limited experiments, and all of them are within the protection scope of the appended claims of the present application. Therefore, the protection scope of the patent of the present application should be based on the content of the appended claims, and the description and drawings can be used to explain the content of the claims.

Claims

1. A microfluidic chip, characterized in that, It includes a sample inlet chamber, a first heating chamber, a second heating chamber, a collection chamber, microchannels for connecting the various chambers, and a heating mechanism; The injection chamber includes a first injection chamber, a second injection chamber, a third injection chamber, and a fourth injection chamber; The first heating chamber, the second heating chamber, and the collection chamber are sequentially connected through the microchannel; The first injection chamber and the second injection chamber are located upstream of the first heating chamber and are both connected to the first heating chamber; The third injection chamber is connected to a microchannel that connects the first heating chamber and the second heating chamber; The fourth injection chamber is located downstream of the first heating chamber and upstream of the second heating chamber, and the fourth injection chamber is connected to the second heating chamber. The heating mechanism is used to independently heat the first heating chamber and the second heating chamber; The first injection chamber and the second injection chamber are connected to the first heating chamber after the microchannels upstream of the first heating chamber are merged. The microchannel communicating with the fourth injection chamber is merged with the microchannel used to connect the first heating chamber and the second heating chamber and then communicates with the second heating chamber. The microchannels used to connect the first heating chamber and the second heating chamber are in the shape of a serpentine tube. The connection point between the third injection chamber and the microchannel connecting the first heating chamber and the second heating chamber is located at the upstream end of the bend of the serpentine microchannel. The second heating chamber has multiple independent sub-cavities. The solution entering the second heating chamber is heated by being diverted through the multiple sub-cavities and then merged into the collection chamber. The number of compartments is 6 to 10; The width of each of the described cavities is consistent.

2. A method for synthesizing magnetic nanoparticles, characterized in that, The microfluidic chip as described in claim 1 is used for synthesis.

3. The method for synthesizing magnetic nanoparticles according to claim 2, characterized in that, include: FeCl3 solution and FeCl2 solution are added to the first injection chamber and the second injection chamber, respectively; a solution with pH greater than 7 is added to the third injection chamber; and an oil phase is added to the fourth injection chamber. The first heating chamber and the second heating chamber are subjected to heating treatment; The reaction products are collected from the collection chamber.

4. The method for synthesizing magnetic nanoparticles according to claim 3, characterized in that, When heating the first heating chamber and the second heating chamber, the temperature inside the first heating chamber is controlled to be 45℃~55℃, and the temperature inside the second heating chamber is controlled to be 65℃~75℃.

5. The method for synthesizing magnetic nanoparticles according to claim 3, characterized in that, The injection flow rate of the first injection chamber is 0.4 mL / min to 0.6 mL / min, the injection flow rate of the second injection chamber is 0.2 mL / min to 0.3 mL / min, the injection flow rate of the third injection chamber is 0.4 mL / min to 0.6 mL / min, and the injection flow rate of the fourth injection chamber is 0.5 mL / min to 1.5 mL / min.

6. The method for synthesizing magnetic nanoparticles according to any one of claims 3 to 5, characterized in that, The solution with a pH greater than 7 includes one or both of ammonia water or NaOH solution with a volume concentration of 2%. The oil phase includes one or both of liquid paraffin and silicone oil.

7. A magnetic nanoparticle, characterized in that, The magnetic nanoparticles were prepared using the method described in any one of claims 2 to 6.

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